TIPS-19 TRIAL IN PROGRESS: SECONDARY BRAIN METASTASES PREVENTION AFTER ISOLATED INTRACRANIAL PROGRESSION ON TRASTUZUMAB/PERTUZUMAB OR T-DM1 IN PATIENTS WITH ADVANCED HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2+ BREAST CANCER WITH THE ADDITION OF TUCATINIB (BRIDGET)

Abstract Despite trastuzumab-based therapy, up to half of patients with HER2+ metastatic breast cancer (MBC) will develop brain metastases (BrM). First-line therapy for MBC, taxane/trastuzumab/pertuzumab (TP), demonstrates poor permeability. Isolated relapse stable/absent extracranial disease remains a clinical problem in both the adjuvant and settings, current guidelines recommend continuing systemic following local therapy. Tucatinib, brain-penetrable HER2-inhibitor, when added trastuzumab capecitabine improves intracranial PFS OS stable/active BrMs. We hypothesize that adding tucatinib TP or T-DM1 MBC isolated progression could delay prevent development further lesions improve OS. BRIDGET (NCT05323955) is single arm, phase II study after progression. A total 48 at 9 U.S. sites through HCRN be enrolled 1st 2nd BrM relapse/progression within 8 weeks Patients must currently receiving setting, recurrence. Extracranial stable per RECISTv1.1 absent. receive their The primary objective compared historical control (H0: iPFS <5 months (mos), HA: >8 mos) HER2CLIMB trial. In these patients, median time from second progression/death was 7.6 mos versus 3.1 arm. Secondary endpoints include by RECISTv1.1, disease, locally treated new distant metastasis PFS, site first progression, OS, toxicity. Collection correlative specimens patient-reported outcomes (FACT-BR, FACIT-Fatigue) are also included.